The majority of the .beta.-receptor blockers therapeutically applied these days are aryloxypropanolamines. Additionally, some are arylethanolamines. Common to both types is an aryl group, i.e. an aromatic system. According to the current opinion of researchers, this aromatic system is a pre-requisite for achieving the desired therapeutic effect (see for example E. Schroder, C. Rufer, R. Schmiechen, Pharmazeutische Chemie, Thieme Verlag 1982, p. 682 ff).
In initial attempts to break through this principle, a possibility was indicated by compounds, in which the aromatic system was "extended outwards" by means of a conjugated double bond. Examples can be found in the following documents: U.S. Pat. No. 4,469,706, DE-OS No. 2 651 084 and EP 31 266.
Subsequently, substances with purely aliphatic basic structures were also manufactured, including substituted oxime ethers, for example J. Med. Chem. 23, 620 (1980); J. Med. Chem. 27, 1291 (1984); J. Med. Chem. 28, 153 (1985); J. Med. Chem. 28, 896 (1985); DE-OS No. 2 658 762; DE-OS No. 2 658 938; EP 37 777; EP 87 378. However, such compounds have had no therapeutic impact so far.
None of the prior art substances have a bicyclic basic structure, let alone one with hetero atoms in the bicyclic ring system. Also, the derivatives known from the literature have no further functional groups in the molecule which could modify or contribute to the overall therapeutic effect. Such added effect was not expected. In the literature, many examples can be found for failed attempts to combine two or more so-called "pharmacophoric groups" in one molecule. In the majority of cases this procedure, occasionally referred to as "chemical hybridisation" or "intramolecular combination", results in the loss of all pharmacological efficacy. The presence of different groups, which are considered pharmacolologically active, in one and the same molecule seems to lead mainly to an extinction of activity (see for example B. J. Nicolaus, "Symbiotic Approach to Drug Design", in "Decision Making in Drug Research", Edit. F. Gross, Raven Press, 1983, p. 173 ff.).
It can therefore be regarded as surprising, that this prejudice does not apply to the compounds according to the present invention. These distinguish themselves by a basic structure (2,6-dioxabicyclo-[3.3.0]octanone) hitherto not utilized in this field of indication, and additionally by the presence of both a nitrate ester group and an N-substituted 3-amino-2-hydroxypropyl-oxime ether function. Despite this chemical hybridization, the invention allowes for the creation of pharmaceutically active substances with novel structures, extending the range of application of known compound classes and exploiting new areas of pharmaceutical indication. Completely unexpectedly, the present compounds exhibit a pharmacological efficacy profile that generally can not be matched by other prior art substances.